We studied bone lesion alterations in three patients with diffuse cutaneous leishmaniasis (DCL) by imaging exams (radiography and scintigraphy) and histopathology. Two patients had bone lesions of distal extremities of hands and feet, and one infiltrating plaques in the skin. The study was conducted at three specialized centers (Presidente Dutra Hospital/Nucleus of Tropical Pathology, UFMA-MA; Gonc¸alo Moniz Research Center-FIOCRUZ-BA; Laboratory of Pathology of Infectious Diseases (LIM-50), University of S˜ao Paulo, SP). Three-phase bone scintigraphy demonstrated high sensitivity and specificity for bone lesions, showing increased uptake of the radiopharmaceutical at sites of active lesions. In contrast, radiography demonstrated lytic lesions, cortical destruction and local osteopenia of the bone extremeties in two patients. Histopathological analysis showed sequestration with presence of amastigote forms of Leishmania (osteomyelitis), mononuclear cells and macrophages containing amastigote forms of Leishmania in one patient. These preliminary data indicate that imaging exams (radiography and scintigraphy) are important in the evaluation of bone lesions in diffuse cutaneous leishmaniasis and should be included in the routine histopathological diagnosis of the disease and follow-up of bone lesions